CN102861124B - A kind of Radix Aucklandiae composition of medicine and application thereof - Google Patents
A kind of Radix Aucklandiae composition of medicine and application thereof Download PDFInfo
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- CN102861124B CN102861124B CN201210418034.3A CN201210418034A CN102861124B CN 102861124 B CN102861124 B CN 102861124B CN 201210418034 A CN201210418034 A CN 201210418034A CN 102861124 B CN102861124 B CN 102861124B
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Landscapes
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Abstract
The Radix Aucklandiae provided by the invention extracts the combination of stilbene and Radix Ginseng extract, its fully displaced volatile oil of Radix Aucklandiae with the compound action of the Radix Astragali, Radix Ginseng, in treatment arrhythmia and GI nerves functional disease, there is good activity.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition, relate to a kind of Radix Aucklandiae composition of medicine and application thereof in particular.
Technical background
The Radix Aucklandiae is one of common drug in circulation of qi promoting Chinese medicine.Compendium of Material Medica day: " Radix Aucklandiae is the medicine of three burnt edema caused by disorder of QI, can be elevated all gas." its nature and flavor acrid, bitter, warm, return spleen, large intestine, gallbladder meridian, pain relieving in effect circulation of qi promoting tune." Japan hanako materia medica " day: " control all gas of trusted subordinate, bladder cold type of pain, vomiting and regurgitation, cholera, has loose bowels, dysentery, and strengthening the spleen to promote digestion is antiabortive." be clinically mainly used in the cards such as dyspepsia caused by stagnation of QI in spleen and stomach, diarrhoea, dysentery stomachache and the dampness-heat in the liver and gallbladder stagnation of QI.The Radix Aucklandiae, containing volatile oil and the saussurine such as α, β-costene, costol, costic acid, lauro lene, constuslactone, can reduce intestinal tube tonicity, and can the contraction that causes of antagonism acetylcholine, plays the effect removing spasm; This medicine also has cardioexcitatory effect, also has certain inhibition to Bacillus typhi, dysentery bacterium, escherichia coli and multiple fungus.In clinical practice uses, if the Radix Aucklandiae uses from different compatibility of drugss, often can play and act on more widely.The impact that Wang Xuan etc. disclose a kind of Radix Aucklandiae and the Radix Astragali in June, 2011 compositions at Chinese Chinese medicine magazine is expressed callus thickness in the early stage fracture of radius agglutination of experimental SD rat and BMP-2, the Therapeutic Method that discussion fracture three phase is dialectical.The Radix Aucklandiae and Radix Astragali compatibility can significantly improve the expression of SD rat early stage fracture of radius broken ends of fractured bone local BMP-2, increase callus thickness, just promote that in SD fracture healing in rats process with regard to BMP-2 expressional function, vital energy regualting and blood circulation-promoting method may be that extremity closed fracture has therapeutical effect in early days.Patent CN101757278B discloses a kind of containing Radix Aucklandiae treatment gastrointestinal disease Chinese medicine composition and preparation method thereof.It is through being processed into by ten flavour of a drug such as the Radix Aucklandiae, Fructus Amomi or Lignum Aquilariae Resinatum, Fructus Aurantii or Fructus Aurantii Immaturus, Lignum Santali Albi, Radix Et Rhizoma Rhei, Cortex Magnoliae Officinalis, Moschus, Semen Crotonis Pulveratum, Fructus Jujubae, Rhizoma Chuanxiongs.The disease such as primary treatment acute diarrhea, irritable bowel syndrome clinically.Patent CN101757083B the present invention relates to treatment gastrointestinal disease Chinese medicine composition containing costunolide and preparation method thereof.It is by costunolide, naringin, total santalol, chrysophanol, artificial Moschus, ligustrazine, and based on Oleum Tiglii and jujube polysaccharide, square medicine adds that other drug is made.The disease such as primary treatment acute diarrhea, irritable bowel syndrome clinically.
Summary of the invention
Research finds, costunolide and dehydrocostuslactone are volatilization maiies body of oil, costunolide and the fragrant lactone of dehydrogenation art have relaxing smooth muscle and spasmolysis, and costunolide has function of gallbladder promoting and suppresses ulcer function, and costunolide can suppress the aorta contraction etc. of being induced by KCI.The present invention by the Radix Aucklandiae respectively with Radix Ginseng and Radix Astragali compatibility.Obtain the drug regimen that two kinds take the Radix Aucklandiae as skeleton medicine, concrete summary of the invention is:
A kind of Radix Aucklandiae composition of medicine, described formula comprises the supercritical extract of the Radix Aucklandiae.
Described formula also comprises the extract of the Radix Astragali.
The described Radix Aucklandiae, Radix Astragali crude drug weight ratio are 5-20:2-15.
The crude drug weight ratio of the described Radix Aucklandiae, the Radix Astragali, Radix Ginseng and the Rhizoma Atractylodis Macrocephalae is 1:1.
Described formula also comprises the extract of Radix Ginseng.
The described Radix Aucklandiae, ginseng raw medical material weight ratio are 5-20:2-15.
The described Radix Aucklandiae, ginseng raw medical material weight ratio are 1:1.
The supercritical extract of the described Radix Aucklandiae is for adopting SFE-CO
2extract Radix Aucklandiae medical material, obtain the supercritical extract of the Radix Aucklandiae, wherein entrainer is dehydrated alcohol.
The application of above-mentioned arbitrary described Radix Aucklandiae composition of medicine in preparation treatment arrhythmia disorder agent.
The application of above-mentioned arbitrary described Radix Aucklandiae composition of medicine in preparation treatment GI nerves functional disease medicine.
Advantageous Effects of the present invention is: the Radix Aucklandiae provided by the invention extracts the combination of stilbene and Radix Ginseng extract, its fully displaced volatile oil of Radix Aucklandiae with the compound action of the Radix Astragali, Radix Ginseng, in treatment arrhythmia and GI nerves functional disease, there is good activity.
Detailed description of the invention
The preparation of embodiment 1 Radix Aucklandiae composition of medicine
Take the Radix Aucklandiae crude drug of the pulverizing of 10.0kg drying, dose respectively in supercritical extraction reactor, follow procedure heats up and pressurizes, and carries out dynamic extraction, CO
2flow is 4.6Lh
-1, extraction temperature 55 DEG C, extracting pressure 25MPa, employing dehydrated alcohol is entrainer, and entrainer consumption is 2mLg
-1, quantitatively pump into entrainer, extraction time 100min; Analytically product collected by still, reclaim under reduced pressure organic solvent, and obtains brown yellow oil extract, as Radix Aucklandiae extract.
Use 50-80% ethanol as the solvent percolation Radix Astragali and Radix Ginseng respectively, solvent consumption is 5-10 times of medical material weight, obtains Radix Astragali extract and Radix Ginseng extract respectively.
Be that 1:3 is mixed to get Radix Aucklandiae composition of medicine I by Radix Aucklandiae extract, Radix Astragali extract by crude drug weight ratio.
Be that 10:1 is mixed to get Radix Aucklandiae composition of medicine II by Radix Aucklandiae extract, Radix Astragali extract by crude drug weight ratio.
Be that 1:1 is mixed to get Radix Aucklandiae composition of medicine III by Radix Aucklandiae extract, Radix Astragali extract by crude drug weight ratio.
Be that 1:3 is mixed to get Radix Aucklandiae composition of medicine IV by Radix Aucklandiae extract, Radix Ginseng extract by crude drug weight ratio.
Be that 10:1 is mixed to get Radix Aucklandiae composition of medicine V by Radix Aucklandiae extract, Radix Ginseng extract by crude drug weight ratio.
Be that 1:1 is mixed to get Radix Aucklandiae composition of medicine VI by Radix Aucklandiae extract, Radix Ginseng extract by crude drug weight ratio.
Embodiment 2 Radix Aucklandiae composition of medicine is investigated the activity of bradycardia rat
Select healthy adult Wistar rat, body weight 250g-300g, before experiment, animal via test confirms behavior without exception.Rat is fed after 7d at adaptability, every day buttocks subcutaneous injection hydrocortisone, every day, 25mg/kg, injected 14d continuously.And when experiment the 2nd week, force rat every day at the upper and lower noon respectively to swim 1 time, to unable be about to time pull out, to induce overstrain, continue 1 week.Observe rat gross morphology, all appearance activities reduce, lassitude, bradykinesia, and the back of a bow is rolled up, amount of drinking water reduces, to lose weight etc. kidney yang deficiency of vital energy symptom for modeling successfully.Select the successful rat of modeling 620, be divided into Radix Aucklandiae composition of medicine I group, Radix Aucklandiae composition of medicine II, Radix Aucklandiae composition of medicine III and Radix Aucklandiae composition of medicine IV, Radix Aucklandiae composition of medicine V and Radix Aucklandiae composition of medicine VI at random, righting helps arteries and veins mixture matched group, model control group, often organize each 12, choosing 12 healthy rats is again blank group, often organizes male and female half and half, sub-cage rearing.After modeling success, next day starts pharmaceutical intervention.Blank group and model group routine feeding, by rat body weight with 20ml/kg dosage with distilled water gavage.Righting helps the drug level of arteries and veins side's decoct group to be respectively 20ml/kg, and administration group dosage is 35g crude drug extract/kg, often organize all in every day the morning 10 time gastric infusion once, treat 14d continuously.
The general state of each treated animal in modeling, medication is observed; Detecting ECG; The changes of contents of cAMP in plasma and cGMP.Experimental data adopts the process of SPSS14.0 statistical software, and all data all adopt mean ± standard deviation
represent.
Naive animals shows as: hair is smooth, the eyes are bright and piercing, reacts, activity is active and intelligent, calls loud, drinking-water of normally taking food.Lethargy is in various degree there is in model group and each treatment group rat when experiment 1ld ~ 14d, to ingest minimizing, growth retardation loses weight, hair is uninteresting lax, cold extremities, and health is very thin, happiness is rolled up and is flocked together, shallow breathing, the kidney yang deficiency of vital energy symptoms such as diarrhea, particularly model control group is more remarkable.
Administration the 14th day, after administration, 1h is with ether light anaesthesia rat at its lower extremity subcutaneous implantation electrode, records clear-headed rear standard II lead electrocardiogram of rat.Within 15th day, give each group of rat skin lower injection with clonidine hydrochloride 2mg/kg, and simultaneously gastric infusion, 0.5h, lh, 1.5h, 2h electrocardiosignal after record gavage, statistical analysis rat heart rate, the rhythm of the heart, atrioventricular block situation of change.
Radix Aucklandiae composition of medicine and water extraction Radix Aucklandiae composition of medicine 1 group as shown in table 1 on the impact of bradycardia rat heart rate, result shows, Radix Aucklandiae composition of medicine I group, water extraction Radix Aucklandiae composition of medicine 1 group, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan amount group and righting help arteries and veins decoct group can improve bradyarrhythmia rat heart rate.
The table 1 respectively group rat rhythm of the heart compares
Note: compare with model group:
△p ﹤ 0.05,
▲p ﹤ 0.01; Compare with blank group:
◇p ﹤ 0.05,
◆p ﹤ 0.01;
After experiment terminates, broken end is got blood, is taken out heart immediately, prepares myocardial homogenates, detects cAMP and cGMP content in myocardial homogenates by test kit regulation.
As shown in table 2, compare for each group, Radix Aucklandiae composition of medicine I-VI group and righting help arteries and veins decoct group cAMP content to be improved, and cGMP level has decline, especially remarkable with Radix Aucklandiae composition of medicine IV group.
The comparison of the concentration of rat plasma cAMP and cCMP respectively organized by table 2
Note: compare with model group:
△p ﹤ 0.05,
▲p ﹤ 0.01; Compare with blank group:
◇p ﹤ 0.05,
◆p ﹤ 0.01;
Bradyarrhythmia is common clinical disease, show as shortness of breath and palpitation in various degree, sensation of oppression and faint pain in the chest, dizzy weakly, dynamic then to increase the weight of, repeatedly fainting history appears in severe patient, burst tic, pareordia severe pain, can Complicated by Heart Failure, cardiogenic shock, cardiac sudden death etc.
CAMP and cardiac function positive correlation, when p1 receptor agonism on heart, produce a large amount of cAMP in cell, heart rate speeds thereupon, and atrioventricular conduction time shortens, and myocardial contraction increases.CAMP promotes steatolysis, glycogenolysis, myocardial contraction, and cGMP is on the contrary.CAMP and cGMP is a pair not only mutually antagonism but also the bioactive substance of mutual dependence for existence---second message,second messenger in body.They are prevalent in biological cell and with in body fluid, regulate body cell intracellular metabolic and various physiological activity.Think that they play important regulating action to the function of myocardial cell, vascular smooth muscle cell at present, its plasma concentration ANOMALOUS VARIATIONS has important function in cardiovascular disease generating process.Therefore the balance of cAMP and cGMP is the critical substances regulating body, and affects the intermediate hub of globality mechanism cell function.CAMP declines, and cGMP raises, and be one of specific pathologies change of generally acknowledged yang deficiency syndrome, the balance and stability of both maintenances is significant in bradycardic treatment.When m receptor is exciting, make K
+outflow increases, and suppresses adenyl cyclase, and the content of cGMP increases, and promote that platelet is built up, make Cardiac depression, its content can reflect the change of atrial pressure indirectly, can judge degree of heart failure thus.Fang Zhongyong Radix Pseudostellariae isothermal kidney yang-tonifying medicinal is treated, and the not method adopting classification to extract effective site is extracted effective ingredient in composition medicine, cAMP can be made to go up and cGMP declines, compare with model group, dosage group and righting help arteries and veins mixture group cAMP level to be improved, cGMP level all has decline, and its difference has significance.Consistent with the result about reporting, show that Radix Aucklandiae composition of medicine I can promote the yang blood and qi of body internal organs, deficiency and excess good and evil tend to be balanced gradually, improve the environment of yang deficiency rat disorder, impel yang deficiency rat to normal development.Radix Aucklandiae composition of medicine I can improve the bradycardia Cardiac Function in Rat and metabolism of myocardium that are caused by deficiency of heart-YANG and kidney-YANG, is conducive to promoting the nutriture of heart sinuatrial node, improving sinus node function, is to improve cardiac function, treat bradycardic effective preparation.
The activity of embodiment 4 Radix Aucklandiae composition of medicine I pair of tachycardia rat is investigated
Get healthy rat 60, male and female are not limit, and average weight is (200 ± 10) g.Divide 6 groups.First group is model group; Second group is Xinluning tablet tablet matched group, and gavage gives the normal saline solution (210mg/10ml) of medicine Xinluning tablet tablet.3rd group is Radix Aucklandiae composition of medicine I group, and gavage gives the normal saline solution (raw medicinal herbs, 875mg/10ml) of Radix Aucklandiae composition of medicine I; 4th group is water extraction Radix Aucklandiae composition of medicine 1 group, gavage gives the normal saline solution (raw medicinal herbs of water extraction Radix Aucklandiae composition of medicine 1 group, 1275mg/10ml), 5th group is commercially available Renshen Guipi Wan group, gavage gives the normal saline solution (raw medicinal herbs, 1275mg/10ml) of commercially available Renshen Guipi Wan, and the 6th group is commercially available GUIPI WAN group, gavage gives the normal saline solution (raw medicinal herbs, 1275mg/10ml) of commercially available GUIPI WAN.Each group all by 2ml/ amount administration only.After administration, first by rat urethane (1.2gkg
-1) intraperitoneal anesthesia, be then fixed on operating-table.Connect electrocardioscope, record II is led, to observe electrocardio change (chart speed 50mm/s).At tail vein injection aconitine (20 μ gml
-1) before, record normal ECG.Inject aconitine after each group of administration 1h, observe electrocardio situation of change.Experimental result is in table 3.
The result of the anti-Aconitine Induced ventricular tachycardia of table 3 Radix Aucklandiae composition of medicine I
Get healthy guinea pig 60.Male and female are not limit, and average weight is (200 ± 10) g.Divide 6 groups.First group is model group; Second group is Xinluning tablet tablet matched group, and gavage gives the normal saline solution (210mg/lOml) of medicine Xinluning tablet tablet, and 2ml/ only.3rd group is Radix Aucklandiae composition of medicine I group, and gavage gives the normal saline solution (raw medicinal herbs, 875mg/10ml) of Radix Aucklandiae composition of medicine I; 4th group is water extraction Radix Aucklandiae composition of medicine 1 group, gavage gives the normal saline solution (raw medicinal herbs of water extraction Radix Aucklandiae composition of medicine 1 group, 1275mg/10ml), 5th group is commercially available Renshen Guipi Wan group, gavage gives the normal saline solution (raw medicinal herbs, 1275mg/10ml) of commercially available Renshen Guipi Wan, and the 6th group is commercially available GUIPI WAN group, gavage gives the normal saline solution (raw medicinal herbs, 1275mg/10ml) of commercially available GUIPI WAN.3ml/ only.After administration, with urethane (1.2gkg
-1) by Cavia porcellus intraperitoneal anesthesia, face upward position and be fixed on operating-table, needle electrode is inserted extremity subcutaneous, and be connected with electrocardiograph, record II leads to observe electrocardio change (chart speed 50mms
-1).At vena femoralis injection cedilanid (0.82mlkg
-1) before, record normal electrocardio.Then vena femoralis injection cedilanid (0.82mlkg
-1), observe electrocardio situation of change, till arrhythmia is recovered normally; Inject cedilanid (0.82mlkg) after matched group administration lh, observe electrocardio situation of change.Experimental result is in table 4.
The result of the anti-Aconitine Induced ventricular tachycardia of spleen side's composition of medicine I returned by table 4
From experimental result, Radix Aucklandiae composition of medicine I has stronger inhibitory action to drug-induced arrhythmia, and when effective dose, electrocardio keeps normal condition not to be any change always; The accidental ventricular premature contraction of Xinluning tablet gavage group or premature ventricular beat, disappear after a time, and the rhythm of the heart recovers normal.Result also shows, Radix Aucklandiae composition of medicine I is better than other drug on the continuous action time.
Aconitine causes ARR main mechanism to be: the sodium channel that have activated myocardial cell, makes sodium channel open, accelerates myocardial cell Na
+interior stream, impels membrane depolarization, accelerates Pacemaker cardiac self-disciplining, brings out ectopic rhythm point, can form polyphyly ectopic rhythm, shorten myocardium refractory stage, and cause arrhythmia.Experimental result shows, Radix Aucklandiae composition of medicine I can suppress the arrhythmia caused by aconitine effectively.
Cardiac glycoside medicine (as cedilanid) can suppress Na on myocardial cell membrane time poisoning
+-K
+-ATP enzyme, thus reduce K
+to intracellular active transport, cause lacking K in cell
+, the maximum diastolic potential of cardiac muscle is reduced, and relaxing period spontaneous depolarization speed is accelerated, and self-disciplining raises, and arrhythmia occurs.Adopt several different drug-induced dissimilar arrhythmia effectively can simulate clinical symptoms, the curative effect of reflection medicine.Result shows, Radix Aucklandiae composition of medicine I can prevent and treat arrhythmia effectively.
The activity of embodiment 5 Radix Aucklandiae composition of medicine I pair of Beagle dog arrhythmia is investigated
The choice criteria of arrhythmia Beagle dog: have selected 4 beagle dogs and study, male and female half and half, about body weight 10kg, monthly age 6-12 month.Beagle dog through at least 5 times (every other day) II lead electrocardiogram (ECG) check and meet following condition person: 1. sinus P ripple, the R-R cycle is not etc., ORS is had after P crosses, periodic inequality >0.16 second, P-R interval, is fixed and >O.12 second, irrelevant with breathing; 2. there are more than 3 long R-R cycles in 10 R-R cycles, observes and without improver, be defined as arrhythmia through one week.Continuous 5 times (every other day 1 time) being had an electro-cardiogram inspection, then being got rid of as once do not met above-mentioned choice criteria person.Arrhythmia condition improved, electrocardiogram obviously improves and meets following two is effective: 1. R-R periodic inequality reduces and close to 0.16 second, P-R interval was fixed and <O.12 second; 2. arrhythmia number of times reduces: occur in 10 R-R cycles that the number of times in long R-R cycle obviously reduces.Electrocardiogram is invalid without being improved as.Experiment is established Radix Aucklandiae composition of medicine I group (A group) (crude drug 3.75g/kg) and water extraction Radix Aucklandiae composition of medicine 1 group (B group) (crude drug 3.75g/kg), every day 9am and 4pm timed drug administrations, first medicine is made into certain density suspension to add in 1/3 feedstuff and mix, dog is allowed to have eaten voluntarily, and then give all the other 2/3 feedstuffs, continuous 17d.
ECG inspection method: dog takes from right erect position, the subcutaneous insertion needle electrode of extremity, measures II lead electrocardiogram after quiet under waking state before food.
To observe after medicine 1,3,5,7,8,9, l1,13,15, the electrocardiogram of 2d after 17d and drug withdrawal: P-R interval, QRs interval, Q-T interval, P ripple, Q ripple, R ripple, s ripple, T ripple, ST section, heart rate and the rhythm of the heart, and with medicine before compare.
Table 5 Radix Aucklandiae composition of medicine I is on the impact of arrhythmia Beagle dog P-R interval and heart rate
The impact of table 6 Radix Aucklandiae composition of medicine I on arrhythmia Beagle dog R-R periodic inequality (s)
*decline percentage rate: R-R periodic inequality after R-R periodic inequality-medicine before medicine
From table 5, >0.12 second before P-R interval medicine, after medicine, 3d rises and is improved to 17d, and P-R asks phase equal <0.12 second, and 2d after lasting till drug withdrawal.Radix Aucklandiae composition of medicine I group and water extraction Radix Aucklandiae composition of medicine 1 group all can improve the heart rate of arrhythmia dog, and after medicine, 9d plays efficacy stability, and maintain a period of time and level; And P wave of electrocardiogram, Q cross, R ripple, S ripple, QRS interval, Q-T interval, no matter be that Radix Aucklandiae composition of medicine I group or water extraction Radix Aucklandiae composition of medicine 1 group all have no significant effect.
From table 6, before administration, the R-R periodic inequality of four dogs is 0.48 ~ 0.53s, and be far longer than 0.16s, after medicine, 1d rises, and the R-R periodic inequality of 2 dosage groups all starts to shorten, and reduce to 040s from 0.48 ~ 0.53s before medicine, its range of decrease is 15% ~ 25%; After medicine, 5 ~ 11d, R-R periodic inequality all obviously shortens, and reduces to 0.20 ~ 0.27 second, and the range of decrease is 44 ~ 62%; After medicine, 13 ~ 15d, R-R periodic inequality is close to normally (close to 0.16s, Radix Aucklandiae composition of medicine I group 13d after medicine is 0.16s; Water extraction Radix Aucklandiae composition of medicine 1 group 15d after medicine is 0.17s.After drug withdrawal 2d, two groups are respectively 0.20s and 0.08s, and its range of decrease is respectively 62% and 83%.
Table 7 Radix Aucklandiae composition of medicine I is on the impact of arrhythmia Beagle dog rhythm of the heart occurrence frequency (long R-R cycle/10 R-R cycles)
From table 7, before administration, four ARR occurrence frequencies of dog are in 10 R-R cycles, occur 4 long R-R cycles.After medicine, 3-5d plays Radix Aucklandiae composition of medicine I group and water extraction Radix Aucklandiae composition of medicine 1 group and all starts to reduce, and is 2-3.5; After medicine, 7-13d obviously reduces, and is 1.5-2.5; After medicine, 15-17d is kept to 1-2, and drug withdrawal 2d reduces to 1, illustrates that Radix Aucklandiae composition of medicine I group and water extraction Radix Aucklandiae composition of medicine 1 group can obviously reduce ARR occurrence frequency, and can maintain certain hour after drug withdrawal.
Experimental result shows, Radix Aucklandiae composition of medicine I group and water extraction Radix Aucklandiae composition of medicine 1 group obviously can improve the heart rate of arrhythmia dog, reduce ARR occurrence frequency, have good therapeutical effect to arrhythmia.Select arrhythmia Beagle dog as object of study, because animal is docile, the advantages such as Electrocardioscopy is convenient, its to the observed result of experimental effect closer to clinical.Bringing out in ARR experiment with Bealge dog coronary artery ligation, observe Radix Aucklandiae composition of medicine I pair of arrhythmia equally and have good preventive and therapeutic effect, therefore the same with the result of the animal pathological model that medicine or operation cause with arrhythmia dog, objective equally and accurate to the role of evaluation of antiarrhythmic drug. and be easy to Estimating curative effect.
The activity of embodiment 6 Radix Aucklandiae composition of medicine I pair of rat gastrointestinal tract dysfunction is investigated
GI nerves functional disease is also called functional gastrointestinal disorder, and the clinical main manifestations of Functional Disturbance of Gastrointestinal Tract is diarrhoea, constipation, stomachache and alternating diarrhea and constipation; And with anorexia, asthenia, become thin and the symptom such as agitation.Reserpine belongs to epinephrine nerve block medicine, the catecholamine mediator of exhaustion maincenter and periphery, make sympathetic nervous system function low, parasympathetic nervous system hyperfunctioning, cause autonomic nervous system functional disorder, and then impelling functional gastrointestinal disorder, the reserpine lumbar injection of doses can make rat occur the performance of clinical Functional Disturbance of Gastrointestinal Tract.
Motilin (MTL) is a kind of important braingut petide hormone, is mainly distributed in brain and jejunum, has adjustment gastric motility, promotes the effect of gastric emptying.MTL deficiency can cause gastrointestinal smooth muscle relaxation, stomach tension force and wriggle weakness, and the gastric emptying time extends, liquid retention increases, and shrink time hungry and disappear, intestinal motility weakens, intestinal to xylose and amino acid whose malabsorption, the symptoms such as the concentrated and contractile function suppression of exocrine pancreatic function and gallbladder.Research proves, the Changing Pattern of dynamic observation functional gastrointestinal disorder rat model MTL, find to show as watery diarrhea in early stage (being less than 6d) of modeling process, its MTL content compared with normal matched group obviously increases, and transference cure of suffering from diarrhoea late period, during feces viscous, its content then obviously declines, illustrate functional gastrointestinal disorder and MTL changes of contents closely related.
Healthy male rat is divided into following 5 groups at random by designing requirement, often organizes 20: Normal group: intraperitoneal injection of saline 5ml/ (kgd), gavages distilled water 5ml/ (kgd) simultaneously; Functional gastrointestinal disorder model group: lumbar injection reserpine 0.5mg/ (kgd), gavages distilled water 5ml/ (kgd) simultaneously; Radix Aucklandiae composition of medicine I group: lumbar injection reserpine 0.5mg/ (kgd), gavage normal saline (the crude drug amount 2.5g containing Radix Aucklandiae composition of medicine I simultaneously, lower same)/(kgd): water extraction Radix Aucklandiae composition of medicine 1 group: lumbar injection reserpine 0.5mg/ (kgd), gavages the normal saline containing water extraction Radix Aucklandiae composition of medicine 1 simultaneously; Commercially available GUIPI WAN group: lumbar injection reserpine 0.5mg/ (kgd), gavages the normal saline containing commercially available GUIPI WAN group simultaneously; Commercially available Renshen Guipi Wan amount group: lumbar injection reserpine 0.5mg/ (kgd), gavages the normal saline containing commercially available Renshen Guipi Wan amount group, successive administration 14d simultaneously.Often organize during 6d and get half zoopery detection, get second half zoopery during 14d again and detect.Observe, record the food ration of rat, body weight and feces situation during administration every day.
Testing index and method are: fasting 18h before each group rat experiment detects, 1. motilin (MTL) content detection in blood plasma and narrow intestinal tissue: by the requirement of MTL radioimmunoassay kits, each group of rat eye socket get blood 2ml in 30 μ L aprotiniies (, 30ml10%EDTA is in pipe, 4 DEG C centrifugal, and-70 DEG C store standby survey; After de-cervical vertebra puts to death rat, get jejunal tissue homogenate immediately, 3500r/min is centrifugal, draws supernatant, and-70 DEG C store standby survey; Assay method by specification carries out.2. local intestinal tissue pathologic finding: often organize random selecting 3 rats, perusal gastrointestinal tract changes, and leaves and takes gastrointestinal tissue and does pathologic finding, to get rid of intestinal mucosa inflammatory lesion.
Experimental result adopts t inspection, uses
represent.Concrete outcome is as shown in table 8.
The dynamic amount dynamic change of MTL in table 8 rat plasma and jejunal tissue
Note: with model group ratio,
*p ﹤ 0.05,
*p ﹤ 0.01;
Model group rats occurs that feces is shapeless in 24h after injection reserpine, and occurs that diarrhoea in various degree, crissum are filthy successively, occurs that appetite declines thereupon, during 6d, loose stool more so, and during 9d, loose stool stops gradually, and feces viscous is not well, even there is constipation, anorexia, become thin and day by day increase the weight of.There is above-mentioned symptom in the most rat of the indivedual rat of Radix Aucklandiae composition of medicine I group, water extraction Radix Aucklandiae composition of medicine 1 group of minority rat, commercially available GUIPI WAN group and commercially available Renshen Guipi Wan, and described four groups performance degree comparatively model group rats is light, rats in normal control group health as before, does not show any abnormalities.The perusal of each group of rat gastrointestinal tract mucosa is no abnormal, and pathologic finding is also there are no obvious inflammatory lesion.In sum, Radix Aucklandiae composition of medicine can regulate the gut hormone of experimental functional gastrointestinal disorder rat, significantly improves its gastrointestinal dysfunction symptom, is one of the party's mechanism of action for the treatment of this disease, regulate the approach of gut hormone as the party, still need and do to inquire into further.
Claims (4)
1. a Radix Aucklandiae composition of medicine, is characterized in that: the described mixture for Radix Aucklandiae supercritical extract and Radix Astragali extract;
Described Radix Aucklandiae supercritical extract is for adopting SFE-CO
2extract Radix Aucklandiae medical material, obtain the supercritical extract of the Radix Aucklandiae, wherein entrainer is dehydrated alcohol;
Described Radix Astragali extract is use the 50-80% ethanol of 5-10 times of medical material weight as the solvent percolation Radix Astragali, obtains Radix Astragali extract;
The described Radix Aucklandiae, Radix Astragali crude drug weight ratio are 5-20:2-15.
2. Radix Aucklandiae composition of medicine according to claim 1, is characterized in that: the crude drug weight ratio of the described Radix Aucklandiae, the Radix Astragali is 1:1.
3. the application of the arbitrary described Radix Aucklandiae composition of medicine of claim 1-2 in preparation treatment arrhythmia disorder agent.
4. the application of the arbitrary described Radix Aucklandiae composition of medicine of claim 1-2 in preparation treatment GI nerves functional disease medicine.
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